Academic Journal
View in EDS
Linked Full Text

Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy

Bibliographic Details
Title: Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy
Authors: Kun Du, He Huang
Source: Translational Oncology, Vol 52, Iss , Pp 102247- (2025)
Publisher Information: Elsevier, 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Agonist antibody, CD40, Programmed death-ligand 1, Bispecific antibody, Cancer immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Bispecific antibodies (BsAbs) represent a promising strategy for cancer immunotherapy. Challenges in immunotherapy include inefficient early events in the immune response cycle, such as antigen presentation and T cell priming. Background stimulation of CD40 with agonistic antibodies is a promising strategy to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Assisted by Alphafold2(AlphaFold-Multimer), we developed a humanized CD40 agonistic antibody that exhibits activation only in the presence of cross-linking. It also demonstrates that the current AlphaFold2(AlphaFold2-Multimer) can predict antibody-antigen complexes. Due to the unique epitope, it demonstrates superior activation compared to APX005M (S267E). Building upon this, we created a novel bispecific antibody (anti-PD-L1/CD40 bispecific antibody, referred to as ''BA4415'') designed to activate CD40 signaling specifically in the context of PD-L1 while simultaneously blocking PD-1/PD-L1 signaling. Results from functional evaluations using effector cells revealed the superior biological activity of BA4415 compared to the combination of each monoclonal antibody. BA4415 demonstrated the ability to enhance T-cell cytokine release in vitro assays, exhibiting superior functional attributes compared to the anti-PD-L1 antibody. Furthermore, in humanized transgenic mice challenged with huPD-L1-expressing tumor cells, BA4415 induced superior anti-tumor activity. This novel anti-PD-L1/CD40 bispecific antibody holds potential for strong anti-tumor therapeutic efficacy by selectively restricting CD40 stimulation in tumors.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1936-5233
Relation: http://www.sciencedirect.com/science/article/pii/S1936523324003735; https://doaj.org/toc/1936-5233
DOI: 10.1016/j.tranon.2024.102247
Access URL: https://doaj.org/article/7e50d56d818c4c408e91683a635f049c
Accession Number: edsdoj.7e50d56d818c4c408e91683a635f049c
Database: Directory of Open Access Journals
FullText Links:
  – Type: other
    Url: https://resolver.ebsco.com:443/public/rma-ftfapi/ejs/direct?AccessToken=4509B76E692A8EA3AE30&Show=Object
Text:
  Availability: 0
CustomLinks:
  – Url: https://doaj.org/article/7e50d56d818c4c408e91683a635f049c
    Name: EDS - DOAJ (s8985755)
    Category: fullText
    Text: View record from Directory of Open Access Journals
    MouseOverText: View record from Directory of Open Access Journals
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edsdoj&genre=article&issn=19365233&ISBN=&volume=52&issue=102247-&date=20250201&spage=&pages=&title=Translational Oncology&atitle=Design%20of%20a%20humanized%20CD40%20agonist%20antibody%20with%20specific%20properties%20using%20AlphaFold2%20and%20development%20of%20an%20anti-PD-L1%2FCD40%20bispecific%20antibody%20for%20cancer%20immunotherapy&aulast=Kun%20Du&id=DOI:10.1016/j.tranon.2024.102247
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
Header DbId: edsdoj
DbLabel: Directory of Open Access Journals
An: edsdoj.7e50d56d818c4c408e91683a635f049c
RelevancyScore: 1039
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 1039.240234375
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Kun+Du%22">Kun Du</searchLink><br /><searchLink fieldCode="AR" term="%22He+Huang%22">He Huang</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Translational Oncology, Vol 52, Iss , Pp 102247- (2025)
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Elsevier, 2025.
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2025
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Agonist+antibody%22">Agonist antibody</searchLink><br /><searchLink fieldCode="DE" term="%22CD40%22">CD40</searchLink><br /><searchLink fieldCode="DE" term="%22Programmed+death-ligand+1%22">Programmed death-ligand 1</searchLink><br /><searchLink fieldCode="DE" term="%22Bispecific+antibody%22">Bispecific antibody</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+immunotherapy%22">Cancer immunotherapy</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplasms%2E+Tumors%2E+Oncology%2E+Including+cancer+and+carcinogens%22">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</searchLink><br /><searchLink fieldCode="DE" term="%22RC254-282%22">RC254-282</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Bispecific antibodies (BsAbs) represent a promising strategy for cancer immunotherapy. Challenges in immunotherapy include inefficient early events in the immune response cycle, such as antigen presentation and T cell priming. Background stimulation of CD40 with agonistic antibodies is a promising strategy to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Assisted by Alphafold2(AlphaFold-Multimer), we developed a humanized CD40 agonistic antibody that exhibits activation only in the presence of cross-linking. It also demonstrates that the current AlphaFold2(AlphaFold2-Multimer) can predict antibody-antigen complexes. Due to the unique epitope, it demonstrates superior activation compared to APX005M (S267E). Building upon this, we created a novel bispecific antibody (anti-PD-L1/CD40 bispecific antibody, referred to as ''BA4415'') designed to activate CD40 signaling specifically in the context of PD-L1 while simultaneously blocking PD-1/PD-L1 signaling. Results from functional evaluations using effector cells revealed the superior biological activity of BA4415 compared to the combination of each monoclonal antibody. BA4415 demonstrated the ability to enhance T-cell cytokine release in vitro assays, exhibiting superior functional attributes compared to the anti-PD-L1 antibody. Furthermore, in humanized transgenic mice challenged with huPD-L1-expressing tumor cells, BA4415 induced superior anti-tumor activity. This novel anti-PD-L1/CD40 bispecific antibody holds potential for strong anti-tumor therapeutic efficacy by selectively restricting CD40 stimulation in tumors.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: electronic resource
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 1936-5233
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: http://www.sciencedirect.com/science/article/pii/S1936523324003735; https://doaj.org/toc/1936-5233
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1016/j.tranon.2024.102247
– Name: URL
  Label: Access URL
  Group: URL
  Data: <link linkTarget="URL" linkTerm="https://doaj.org/article/7e50d56d818c4c408e91683a635f049c" linkWindow="_blank">https://doaj.org/article/7e50d56d818c4c408e91683a635f049c</link>
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsdoj.7e50d56d818c4c408e91683a635f049c
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.7e50d56d818c4c408e91683a635f049c
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.tranon.2024.102247
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: Agonist antibody
        Type: general
      – SubjectFull: CD40
        Type: general
      – SubjectFull: Programmed death-ligand 1
        Type: general
      – SubjectFull: Bispecific antibody
        Type: general
      – SubjectFull: Cancer immunotherapy
        Type: general
      – SubjectFull: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
        Type: general
      – SubjectFull: RC254-282
        Type: general
    Titles:
      – TitleFull: Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Kun Du
      – PersonEntity:
          Name:
            NameFull: He Huang
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 19365233
          Numbering:
            – Type: volume
              Value: 52
            – Type: issue
              Value: 102247-
          Titles:
            – TitleFull: Translational Oncology
              Type: main
ResultId 1